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Molecular imaging studies have shown increased striatal dopamine synthesis capacity (DSC) in schizophrenia and people in the prodrome of psychosis. However, it is unclear if genetic risk for psychosis is associated with altered DSC. To investigate this, we recruited healthy controls and two antipsychotic naive groups of individuals with copy number variants, one with a genetic deletion at chromosome 22q11.2, and the other with a duplication at the same locus, who are at increased and decreased risk for psychosis, respectively. Fifty-nine individuals (21 with 22q11.2 deletion, 12 with the reciprocal duplication and 26 healthy controls) received clinical measures and [18F]-DOPA PET imaging to index striatal Ki<jats:sup>cer<\/jats:sup>. There was an inverse linear effect of copy number variant number on striatal Ki<jats:sup>cer<\/jats:sup> value (<jats:italic>B<\/jats:italic>\u2009=\u2009\u22121.2\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>, SE\u2009=\u20092\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), with controls showing levels intermediate between the two variant groups. Striatal Ki<jats:sup>cer<\/jats:sup> was significantly higher in the 22q11.2 deletion group compared to the healthy control (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, Cohen\u2019s <jats:italic>d<\/jats:italic>\u2009=\u20091.44) and 22q11.2 duplication (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, Cohen\u2019s <jats:italic>d<\/jats:italic>\u2009=\u20092) groups. Moreover, Ki<jats:sup>cer<\/jats:sup> was positively correlated with the severity of psychosis-risk symptoms (<jats:italic>B<\/jats:italic>\u2009=\u2009730.5, SE\u2009=\u2009310.2, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and increased over time in the subject who went on to develop psychosis, but was not associated with anxiety or depressive symptoms. Our findings suggest that genetic risk for psychosis is associated with dopaminergic dysfunction and identify dopamine synthesis as a potential target for treatment or prevention of psychosis in 22q11.2 deletion carriers.<\/jats:p>","DOI":"10.1038\/s41380-021-01108-y","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T04:04:20Z","timestamp":1620792260000},"page":"1995-2006","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Striatal dopaminergic alterations in individuals with copy number variants at the 22q11.2 genetic locus and their implications for psychosis risk: a [18F]-DOPA PET study"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2685-1789","authenticated-orcid":false,"given":"Maria","family":"Rogdaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Devroye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariasole","family":"Ciampoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3562-0683","authenticated-orcid":false,"given":"Mattia","family":"Veronese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-7253","authenticated-orcid":false,"given":"Abhishekh H.","family":"Ashok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-2566","authenticated-orcid":false,"given":"Robert A.","family":"McCutcheon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-3659","authenticated-orcid":false,"given":"Sameer","family":"Jauhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Bonoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0464-2065","authenticated-orcid":false,"given":"Maria","family":"Gudbrandsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-3467","authenticated-orcid":false,"given":"Eileen","family":"Daly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese","family":"van Amelsvoort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-3254","authenticated-orcid":false,"given":"Marianne","family":"Van Den Bree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4798-0862","authenticated-orcid":false,"given":"Michael J.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3766-3815","authenticated-orcid":false,"given":"Federico","family":"Turkheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6326-0657","authenticated-orcid":false,"given":"Francesco","family":"Papaleo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver D.","family":"Howes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"1108_CR1","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/S0140-6736(09)60072-6","volume":"373","author":"P Lichtenstein","year":"2009","unstructured":"Lichtenstein P, Yip BH, Bj\u00f6rk C, Pawitan Y, Cannon TD, Sullivan PF, et al. 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ODH has received investigator-initiated research funding from and\/or participated in advisory\/speaker meetings organized by Angellini, Astra-Zeneca, Autifony, Biogen, BMS, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand and Roche. Neither ODH nor his family has been employed by or has holdings\/a financial stake in any biomedical company. MV is consultant for GSK but no competing interests with this work exists. MJO and MVDB report grants from Takeda Pharmaceuticals outside of the submitted work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}